The proposed research will test the applicability of a new method for time-integrating measurement of the tissue availability of hormones, to the ovarian hormone estradiol. The new method uses an ultraminiature device, installed in the mouth of a subject, to continuously accumulate hormones from the saliva. The rate of accumulation at any moment directly reflects the availability o the hormone to tissue. The total accumulation over some time (1 to 10 h) reflects the time integral of hormone availability to tissue. This is advantageous since estradiol levels in the circulation and in the saliva fluctuate widely over short time intervals, and only 1 - 2% of estradiol in blood is actually available to tissue. The new method, if applicable to estradiol, would represent both the most direct and the least invasive way of determining the actual degree of tissue exposure to estradiol. Estradiol is a primary regulator of reproductive physiology, and current estradiol measurements are of some use in predicting the onset of the fertile period and the time ovulation, and predicting the outcome of fertility- enhancement procedures. A more reliable and convenient method for predicting the onset of the fertile period and the likelihood of successful conception and pregnancy would potentially find a wide market. The Phase I research specifically will extend the measurement method to estradiol, applying rigorous in vitro tests of the method under conditions approximating those of the intended use.